Genome-wide association study of polymorphisms predisposing to bronchiolitis

Abstract

<p>Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with<br />later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not<br />well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a genomewide<br />association study (GWAS) in which 5,300,000 single nucleotide polymorphisms (SNPs) were tested<br />for association in a Finnish–Swedish population of 217 children hospitalized for bronchiolitis and 778<br />controls. The most promising SNPs (n = 77) were genotyped in a Dutch replication population of 416<br />cases and 432 controls. Finally, we used a set of 202 Finnish bronchiolitis cases to further investigate<br />candidate SNPs. We did not detect genome-wide significant associations, but several suggestive<br />association signals (p < 10−5) were observed in the GWAS. In the replication population, three SNPs<br />were nominally associated (p < 0.05). Of them, rs269094 was an expression quantitative trait locus<br />(eQTL) for KCND3, previously shown to be associated with occupational asthma. In the additional<br />set of Finnish cases, the association for another SNP (rs9591920) within a noncoding RNA locus was<br />further strengthened. Our results provide a first genome-wide examination of the genetics underlying<br />bronchiolitis. These preliminary findings require further validation in a larger sample size.<br /></p>